Intracerebral recombinant HSV-1 vector does not reactivate latent HSV-1.
Herpes simplex virus type-1 (HSV-1) has been used for gene delivery in the nervous system for the treatment of brain tumors and other neurological diseases. In most protocols, recombinant viruses containing the gene of interest are directly injected into the brain. Since many people harbor latent wild-type HSV-1 virus in sensory ganglia and other regions of the nervous system, there is a potential risk that the injected recombinant virus may reactivate the latent wild-type virus to cause severe encephalitis. The present study used two rat latent infection models to evaluate this risk. Adult rats were infected with wild-type kos by cornea scarification or by intracerebral injection, and after the establishment of latency, the ICP6(-) strain hrR3 was injected intracerebrally. In the control group, the latent virus was reactivated by treatment of cadmium sulfate. Viral shedding from tears was detected by incubation with Vero cells, and the trigeminal ganglia, cortical tissue and the eyes were collected to detect reactivated wild-type virus by RT-PCR. Our results showed that while the reactivated wild-type virus was readily detectable in the cadmium-sulfate-treated animals, intracerebrally infected hrR3 did not reactivate the latent virus in either the corneal model or the cerebral model. These results indicate that intracranial injection of partially defective recombinant virus may bear little risk of reactivating latent wild-type virus harbored in the sensory ganglia or the brain in our animal model.
Wang
Q
Q
Department of Surgery, University of British Columbia, Vancouver, Canada.
Guo
J
J
Jia
W
W
D000818:Animals; D001927:Brain Diseases / Q000821:virology; D019187:Cadmium Compounds; D002540:Cerebral Cortex / Q000821:virology; D003316:Corneal Diseases / Q000821:virology; D004274:DNA, Recombinant; D004195:Disease Models, Animal; D005123:Eye / Q000821:virology; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors / Q000009:adverse effects*; D006566:Herpesviridae Infections / Q000821:virology*; D018259:Herpesvirus 1, Human; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates; D012668:Trigeminal Ganglion / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency
D019187:Cadmium Compounds; D004274:DNA, Recombinant; D013431:Sulfates; C037123:cadmium sulfate